Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes

Phase 4

Recruiting

• Conditions: Type 2 Diabetes
• Interventions: Drug: Semaglutide, 2.0 mg/mL

• Registration Number: NCT05597202
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

To study the effect of type 2 diabetes (T2D) on vascular wall inflammation and hematopoietic stem cell composition in vivo, and whether these changes can be reversed with glucagon like peptide 1 receptor (GLP1R)-agonism.

Detailed Description

We will use 68Ga-Dotatate PET/CT scans, bone marrow aspirations and peripheral blood analyses to determine the effect of type 2 diabetes on vascular wall inflammation, and hematopoietic stem cell composition, and whether these changes can be reversed using high dose semaglutide treatment, up to 2.0mg subcutaneously per week, for a period of six months.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-26
• Study First Posted: 2022-10-27
• Study Start: 2023-01-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-09
• Primary Completion: 2024-03
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Age >50 years old
• Diagnosed with type 2 diabetes
• HbA1c >64mmol/mol

Exclusion Criteria

1. (History of) malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
2. Chronic or recent infections and/or clinical signs of infection and/or a plasma C-reactive protein above 10ng/ml
3. Auto-immune diseases (including type 1 diabetes)
4. Recent or chronic immunosuppressant or antibiotic usage
5. Use of any GLP1R-agonist at baseline or prior intolerance to use of GLP1R-agonists.
6. Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
7. Uncontrolled hypertension (systolic blood pressure > 180mmHg, diastolic blood pressure > 100mmHg)
8. Uncontrolled chronic inflammatory conditions, including gout.
9. Women of childbearing age who are not using effective contraceptives.
10. Heart failure New York Heart Association (NYHA) class IV at screening visit.
11. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) ≥ 2 times the upper limit of normal (ULN) at screening visit.
12. Pancreatitis in medical history.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Semaglutide, 2.0 mg/mL	Will receive semaglutide treatment for 6 months, at the highest tolerable dose, up to a maximum of 2.0mg weekly.

Primary Outcome Measures

Name	Time	Method
Difference in coronary 68Ga-Dotatate uptake after treatment.	6 months	The within subject comparison of 68Ga-Dotatate uptake in the coronary arteries before and after semaglutide treatment, expressed as a difference in TBRmax.

Secondary Outcome Measures

Name	Time	Method
Difference in bone marrow aspirates after treatment.	6 months	The within subject comparison of bone marrow aspirates before and after semaglutide treatment, expressed as a difference in stem cell count.

Trial Locations

Locations (1)

AMC; 🇳🇱 Amsterdam, Noord-Holland, Netherlands